The detailed mechanism of metal-cysteine binding is still poorly understood. It is not clear if every metal cation can induce cysteine deprotonation, how the dielectric medium affects this process, and the extent to which other ligands from the metal's first and second coordination shell influence cysteine ionization. It is also not clear if the zinc cation, with its positive charge reduced by charge transfer from the first two bound cysteinates, could still assist deprotonation of the next one or two cysteines in Cys(3)His and Cys(4) zinc-finger cores. Here, we elucidate the factors governing the cysteine protonation state in metal-binding sites, in particular in Zn.CYS4 complexes, using a combined ab initio and continuum dielectric approach. Transition metal dications such as Zn2+ and Cu2+ and trivalent cations such as Al3+ with pronounced ability to accept charge from negatively charged Cys- are predicted to induce cysteine cleprotonation, but not "hard" divalent cations such as Mg2+. A high dielectric medium was found to favor cysteine deprotonation, while a low one favored the protonated state. Polarizable ligands in the metal's first shell that can competitively donate charge to the metal cation were found to lower the efficiency of the metal-assisted cysteine deprotonation. The calculations predict that the zinc cation could assist deprotonation of all the cysteines during the folding of Cys(4) Zinc-finger cores and the [Zn.(CYS-)(4)](2-) state is likely to be preserved in the final folded conformation of the protein provided the binding site is tightly encapsulated by backbone peptide groups or lysine/arginine side chains, which stabilize the ionized cysteine core.